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Chemical Compound Review

Polaris     2-(bis(phosphonomethyl)amino) ethanoic acid

Synonyms: GLYPHOSINE, Glyphosphine, CHEMBL265954, AG-E-72560, CHEBI:63484, ...
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Disease relevance of GLYPHOSINE

  • Polaris, a protein associated with cystic kidney disease in Tg737(o)(rpk) mice, functions in a ciliogenic pathway [1].
  • Similarities in cyst formation and striking differences in cilia expression associated with these ARPKD mouse models indicates that cyst formation and cilia expression are independent phenotypic features regulated by polaris [2].
  • The Oak Ridge Polycystic Kidney (orpk) mouse contains a mutated Tg737 gene that disrupts expression of polaris, a protein required for ciliogenesis [3].
  • A subsample of 183 men (62 cases and 121 controls) enrolled in the Polaris HIV Seroconversion Study as of June 2001 was analyzed [4].
  • Time-dependent change in fast pathway refractoriness after slow pathway ablation in atrioventricular node reentrant tachycardia. Mansfield Polaris Investigators [5].

Psychiatry related information on GLYPHOSINE

  • Continued sexual risk behavior following repeatedly testing HIV-negative in the Polaris HIV Seroconversion Study (Ontario, Canada) led to this follow-up study which identifies the impact of repeat negative testing among 64 men and women [6].

High impact information on GLYPHOSINE

  • Furthermore, cilia are malformed in mice with PKD with mutations in TgN737Rpw (encoding polaris) [7].
  • When expressed exogenously in polarized renal epithelial cells, cystin is detected in cilia, and its expression overlaps with polaris, another PKD-related protein [8].
  • Little is known about peptide signaling in plant growth; however, Arabidopsis thaliana POLARIS (PLS), encoding a 36-amino acid peptide, is required for correct root growth and vascular development [9].
  • The POLARIS Peptide of Arabidopsis Regulates Auxin Transport and Root Growth via Effects on Ethylene Signaling [9].
  • However, POLARIS was expressed in the basal part of hydra embryos lacking an embryonic root and in the basal parts of both hydra and emb30 seedlings [10].

Biological context of GLYPHOSINE

  • The POLARIS (PLS) gene of Arabidopsis was identified as a promoter trap transgenic line, showing beta-glucuronidase fusion gene expression predominantly in the embryonic and seedling root, with low expression in aerial parts [11].
  • Here we show that in orpk mice, a model system for PKD that harbors a mutation in the gene that encodes the polaris protein, pancreatic defects start to occur at the end of gestation, with an initial expansion of the developing pancreatic ducts [12].
  • Polaris morphants have defects in KV cilia, suggesting that the laterality phenotype is due to problems in cilia function per se [13].
  • To test this hypothesis, we assessed the contribution of Polaris and cilium structure and function to renal epithelial ion transport electrophysiology [14].
  • Marinomonas polaris sp. nov., a psychrohalotolerant strain isolated from coastal sea water off the subantarctic Kerguelen islands [15].

Anatomical context of GLYPHOSINE


Associations of GLYPHOSINE with other chemical compounds


Gene context of GLYPHOSINE

  • This study sought to determine whether the mammalian polycystins are expressed in primary cilia of renal epithelia and whether these proteins co-localize with polaris and cystin, the newly described, cilia-associated protein that is disrupted in the cpk mouse [22].
  • Polaris is involved in ciliary assembly, while Pkd2 is proposed to function as a Ca(2+)-permeable cation channel [13].
  • The intraflagellar transport (IFT) proteins Ift172/Wimple and Polaris/Ift88 and the anterograde IFT motor kinesin-II are required for the production and maintenance of cilia [23].
  • Two genes proposed to be important in this cilia-mediated signaling cascade are polaris and polycystin-2 (pkd2) [13].
  • Genetic analysis shows that Wim, Polaris and the IFT motor protein Kif3a are required for Hedgehog signalling at a step downstream of Patched1 (the Hedgehog receptor) and upstream of direct targets of Hedgehog signalling [24].

Analytical, diagnostic and therapeutic context of GLYPHOSINE


  1. Polaris, a protein disrupted in orpk mutant mice, is required for assembly of renal cilium. Yoder, B.K., Tousson, A., Millican, L., Wu, J.H., Bugg, C.E., Schafer, J.A., Balkovetz, D.F. Am. J. Physiol. Renal Physiol. (2002) [Pubmed]
  2. Delayed cystogenesis and increased ciliogenesis associated with the re-expression of polaris in Tg737 mutant mice. Brown, N.E., Murcia, N.S. Kidney Int. (2003) [Pubmed]
  3. Loss of primary cilia results in deregulated and unabated apical calcium entry in ARPKD collecting duct cells. Siroky, B.J., Ferguson, W.B., Fuson, A.L., Xie, Y., Fintha, A., Komlosi, P., Yoder, B.K., Schwiebert, E.M., Guay-Woodford, L.M., Bell, P.D. Am. J. Physiol. Renal Physiol. (2006) [Pubmed]
  4. Delayed application of condoms is a risk factor for human immunodeficiency virus infection among homosexual and bisexual men. Calzavara, L., Burchell, A.N., Remis, R.S., Major, C., Corey, P., Myers, T., Millson, M., Wallace, E. Am. J. Epidemiol. (2003) [Pubmed]
  5. Time-dependent change in fast pathway refractoriness after slow pathway ablation in atrioventricular node reentrant tachycardia. Mansfield Polaris Investigators. Krahn, A.D., Klein, G.J., Yee, R. The Canadian journal of cardiology. (1997) [Pubmed]
  6. Psychosocial impact of repeat HIV-negative testing: a follow-up study. Ryder, K., Haubrich, D.J., Callà, D., Myers, T., Burchell, A.N., Calzavara, L. AIDS and behavior. (2005) [Pubmed]
  7. Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells. Nauli, S.M., Alenghat, F.J., Luo, Y., Williams, E., Vassilev, P., Li, X., Elia, A.E., Lu, W., Brown, E.M., Quinn, S.J., Ingber, D.E., Zhou, J. Nat. Genet. (2003) [Pubmed]
  8. Cystin, a novel cilia-associated protein, is disrupted in the cpk mouse model of polycystic kidney disease. Hou, X., Mrug, M., Yoder, B.K., Lefkowitz, E.J., Kremmidiotis, G., D'Eustachio, P., Beier, D.R., Guay-Woodford, L.M. J. Clin. Invest. (2002) [Pubmed]
  9. The POLARIS Peptide of Arabidopsis Regulates Auxin Transport and Root Growth via Effects on Ethylene Signaling. Chilley, P.M., Casson, S.A., Tarkowski, P., Hawkins, N., Wang, K.L., Hussey, P.J., Beale, M., Ecker, J.R., Sandberg, G.K., Lindsey, K. Plant Cell (2006) [Pubmed]
  10. Promoter trap markers differentiate structural and positional components of polar development in Arabidopsis. Topping, J.F., Lindsey, K. Plant Cell (1997) [Pubmed]
  11. The POLARIS gene of Arabidopsis encodes a predicted peptide required for correct root growth and leaf vascular patterning. Casson, S.A., Chilley, P.M., Topping, J.F., Evans, I.M., Souter, M.A., Lindsey, K. Plant Cell (2002) [Pubmed]
  12. Orpk mouse model of polycystic kidney disease reveals essential role of primary cilia in pancreatic tissue organization. Cano, D.A., Murcia, N.S., Pazour, G.J., Hebrok, M. Development (2004) [Pubmed]
  13. Polaris and Polycystin-2 in dorsal forerunner cells and Kupffer's vesicle are required for specification of the zebrafish left-right axis. Bisgrove, B.W., Snarr, B.S., Emrazian, A., Yost, H.J. Dev. Biol. (2005) [Pubmed]
  14. Heightened epithelial Na+ channel-mediated Na+ absorption in a murine polycystic kidney disease model epithelium lacking apical monocilia. Olteanu, D., Yoder, B.K., Liu, W., Croyle, M.J., Welty, E.A., Rosborough, K., Wyss, J.M., Bell, P.D., Guay-Woodford, L.M., Bevensee, M.O., Satlin, L.M., Schwiebert, E.M. Am. J. Physiol., Cell Physiol. (2006) [Pubmed]
  15. Marinomonas polaris sp. nov., a psychrohalotolerant strain isolated from coastal sea water off the subantarctic Kerguelen islands. Gupta, P., Chaturvedi, P., Pradhan, S., Delille, D., Shivaji, S. Int. J. Syst. Evol. Microbiol. (2006) [Pubmed]
  16. Expression analyses and interaction with the anaphase promoting complex protein Apc2 suggest a role for inversin in primary cilia and involvement in the cell cycle. Morgan, D., Eley, L., Sayer, J., Strachan, T., Yates, L.M., Craighead, A.S., Goodship, J.A. Hum. Mol. Genet. (2002) [Pubmed]
  17. The C. elegans homolog of the murine cystic kidney disease gene Tg737 functions in a ciliogenic pathway and is disrupted in osm-5 mutant worms. Haycraft, C.J., Swoboda, P., Taulman, P.D., Thomas, J.H., Yoder, B.K. Development (2001) [Pubmed]
  18. Intraflagellar transport is required in Drosophila to differentiate sensory cilia but not sperm. Han, Y.G., Kwok, B.H., Kernan, M.J. Curr. Biol. (2003) [Pubmed]
  19. Comparison of power- and temperature-guided radiofrequency modification of the atrioventricular node. Polaris Investigator Group. Kavesh, N.G., Gosnell, M.R., Shorofsky, S.R., Gold, M.R. Am. J. Cardiol. (1997) [Pubmed]
  20. Intramanchette transport (IMT): managing the making of the spermatid head, centrosome, and tail. Kierszenbaum, A.L. Mol. Reprod. Dev. (2002) [Pubmed]
  21. Effect of polysaccharide extracted from Glaciecola polaris on the protection of mouse macrophages from oxidative injury. Qian, G., Xu, Z. Bioresour. Technol. (2007) [Pubmed]
  22. The polycystic kidney disease proteins, polycystin-1, polycystin-2, polaris, and cystin, are co-localized in renal cilia. Yoder, B.K., Hou, X., Guay-Woodford, L.M. J. Am. Soc. Nephrol. (2002) [Pubmed]
  23. Cilia and Hedgehog responsiveness in the mouse. Huangfu, D., Anderson, K.V. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  24. Hedgehog signalling in the mouse requires intraflagellar transport proteins. Huangfu, D., Liu, A., Rakeman, A.S., Murcia, N.S., Niswander, L., Anderson, K.V. Nature (2003) [Pubmed]
  25. Use of three-dimensional Gaussian interpolation in the projector/backprojector pair of iterative reconstruction for compensation of known rigid-body motion in SPECT. Feng, B., Gifford, H.C., Beach, R.D., Boening, G., Gennert, M.A., King, M.A. IEEE transactions on medical imaging. (2006) [Pubmed]
  26. Seroepidemiological studies of polaris Submarine crews. II. Infectious mononucleosis. Storrie, M.C., Sphar, R.L. Military medicine. (1976) [Pubmed]
  27. Chronic electrical stimulation of the thalamic unspecific activating system in a patient with coma due to midbrain and upper brain stem infarction. Sturm, V., Kühner, A., Schmitt, H.P., Assmus, H., Stock, G. Acta neurochirurgica. (1979) [Pubmed]
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